Pixel-wise point spread function engineering systems and methods

A computer-implemented method for producing an optical mask for an SMOLM imaging system, the method comprising:

• a. providing, to a computing device, a baseline optical mask comprising a plurality of mask pixels distributed at a plurality of mask pixel positions within a mask plane, each mask pixel comprising at least one optical modulation element configured to modulate at least one optical parameter of a photon produced by an emitter propagating therethrough;
• b. providing, to the computing device, a plurality of emitter images indicative of dipole spread functions captured using the SMOLM imaging system provided with the baseline optical mask, each image comprising a plurality of image pixels indicative of a dipole spread function, each image pixel comprising a pixel position and a pixel intensity indicative of a number of photons detected at the pixel position, wherein each emitter image is obtained for a reference emitter positioned at a reference lateral position and at one sample orientation within an orientation space;
• c. determining, using the computing device, a loss function comprising a matrix quantifying variances in precision of emitter orientations estimated from the dipole spread functions from the plurality of images;
• d. iteratively modifying, using the computing device, at least one optical parameter of at least one mask pixel to minimize the loss function to produce the optical mask.